1. Field of the Invention
The present invention generally relates to thiazolhydrazide derivatives and stereoisomeric forms, prodrugs, solvates, hydrates and/or pharmaceutically acceptable salts of these compounds as well as pharmaceutical compositions containing at least one of these thiazolhydrazides derivatives together with pharmaceutically acceptable carrier, excipient and/or diluents. Said thiazolhydrazides derivatives have been identified as specific inhibitors of aggregation of Tau-proteins and are useful for the treatment of Alzheimer's Disease and related neurodegenerative diseases, disorders and conditions.
2. Description of the Relevant Art
Tauopathies belong to the group of neurodegenerative diseases in which accumulation of Tau-protein in the brain is observed. Diseases like Alzheimer Disease, Morbus Pick and Corticobasal Degeneration are well known diseases belonging to this group, wherein the most investigated disease of this group is Alzheimer Disease.
Alzheimer's is the most common form of dementia that gradually destroys brain cells and leads to progressive decline in mental function. This pathological process consists principally of neuronal loss or atrophy mainly in the temporoparietal cortex, but also in the frontal cortex, together with an inflammatory response to the deposition of amyloid plaques and neurofibrillary tangles.
Morbus Pick (Frontotemporal Dementia, FTD, Pick's Disease) is a relatively rarely occurring demential disorder having a prevelence of ca. 2% among all patients suffering from mental disorders. As the name (FTD) suggests Pick's Disease is associated with shrinking of the frontal and temporal anterior lobes of the brain leading to massive change in behaviour and problems with language.
Corticobasal Degeneration is a progressive neurological disorder characterized by nerve cell loss and atrophy of multiple areas of the brain including the cerebral cortex and the basal ganglia.
The use of phenylthiazoles for treating neurodegenerative diseases has been described earlier. WO 2005/035510 A1 and EP 1 223 933 B1 both disclose phenylthiazoles for treatment of Alzheimer's disease and Parkinson's disease.
WO 98/27108 A2 discloses 4-phenylthiazole for treatment of NO-mediated diseases and for Alzheimer Disease.
EP 1 448 553 B1 discloses N-substituted heterocyclic hydrazides having neurotrophic activity for treatment of diseases like Parkinson's Disease, Alzheimer Disease, stroke and multiple sclerosis.
None of these prior art documents disclose the use of the claimed thiazolhydrazides derived compounds described in the present application for the treatment of neurodegenerative diseases.